Related papers: Stability Threshold as a Selection Principle for P…

The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…

Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…

The standard genetic code is known to be much more efficient in minimizing adverse effects of misreading errors and one-point mutations in comparison with a random code having the same structure, i.e. the same number of codons coding for…

We present the results of a self-consistent, unified molecular dynamics study of simple model heteropolymers in the continuum with emphasis on folding, sequence design and the determination of the interaction parameters of the effective…

By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the…

Here we propose that the upper bound marginal stability of proteins (7.4 kcal/mol) is a universal property that includes macro-molecular complexes and is not affected by molecular changes such as mutations and Post-Translational…

Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Machine learning and statistical analysis techniques can inform how to allocate limited resources to the considerable time and…

Inverse folding models have proven to be highly effective zero-shot predictors of protein stability. Despite this success, the link between the amino acid preferences of an inverse folding model and the free-energy considerations underlying…

In this study, we propose an analytic statistical mechanics approach to solve a fundamental problem in biological physics called protein design. Protein design is an inverse problem of protein structure prediction, and its solution is the…

Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…

Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of…

We study the impact of mutations (changes in amino acid sequence) on the thermodynamics of simple protein-like heteropolymers consisting of N monomers, representing the amino acid sequence. The sequence is designed to fold into its native…

In a similar way in which the folding of single--domain proteins provide an important test in the study of self--organization, the folding of homodimers constitute a basic challenge in the quest for the mechanisms which are at the basis of…

We simulate the evolution of model protein sequences subject to mutations. A mutation is considered neutral if it conserves 1) the structure of the ground state, 2) its thermodynamic stability and 3) its kinetic accessibility. All other…

Evolution in time-varying environments naturally leads to adaptable biological systems that can easily switch functionalities. Advances in the synthesis of environmentally-responsive materials therefore open up the possibility of creating a…

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

The standard genetic code is known to be robust to translation errors and point mutations. We studied how small modifications of the standard code affect its robustness. The robustness was assessed in terms of a proper stability function,…

We present an analytical theory for heteropolymer deformation, as exemplified experimentally by stretching of single protein molecules. Using a mean-field replica theory, we determine phase diagrams for stress-induced unfolding of typical…

We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain…

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional…